Dopamine naturally occurring catecholamine

The adrenomimetic drugs, including the naturally occurring catecholamines, initiate their responses by combining with a-, P-, or dopamine adrenoceptors. This interaction triggers a series of biochemical events starting within the effector cell membrane that eventually culminates in the production of a physiological response. 

Dopamine is a naturally occurring catecholamine it is the immediate biochemical precursor of the norepinephrine found in adrenergic neurons and the adrenal medulla. It is also a neurotransmitter in the CNS, where it is released from dopaminergic neurons to act on spe-cihc dopamine receptors (see Chapter 31). 

Disposition in the Body. Dopamine is a naturally occurring catecholamine and is considered to be the metabolic precursor of noradrenaline. It is inactivated after oral administration. It is excreted mainly as 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) noradrenaline and 3-methoxytyramine are also metabolites. Dopamine is a metabolite of levodopa. 

Dopamine is a naturally occurring catecholamine and central neurotransmitter capable of raising cardiac output, reducing peripheral resistance, and specifically increasing renal blood flow. Infusions (generally up to 10 micrograms/kg/hour) have proven valuable in shock and congestive heart failure. 

The three naturally occurring catecholamines dopamine, NE, and epinephrine are used as therapeutic agents. 

The naturally occurring catecholamines dopamine (1), norepinephrine (2), and epinephrine(3) (Figure 1) play key roles in neurotransmission, metabolism, and in the control of various physiological processes. For example, norepinephrine is the primary neurotransmitter in the sympathetic nervous system and also functions as a neurotransmitter in the central nervous system. Epinephrine, elaborated by the adrenal gland, has potent effects on the heart, vascular and other smooth muscles. Dopamine is an important neurotransmitter in the central nervous system, and has important peripheral effects in such organs as the kidney and heart. The importance of these effects has made the search for drugs that can mimic, inhibit, or otherwise modulate the effects of these catecholamines an important area of medicinal chemistry. 

Figure 1 Naturally occurring catecholamines Dopamine (1), norepinephrine (2), and epinephrine (3).

Mimic naturally occurring catecholamines (epinephrine, norepinephrine and dopamine) or stimulate the release of norepinephrine Indications Alpha-adrenergic agonists used to treat hypotension Common drug examples ... 

The naturally occurring catecholamines—dopamine (DA) (1), / -norepinephrine (/ -NE) (2), and / -epinephrine (/J-EPI) (3)— have many imiK)rtant biological functions. These catecholamines are produced in vivo from L-tyrosine. Tyrosine is first converted to dihydroxyphenylalanine (DOPA) by aromatic hydroxylation. L-DOPA is then decarboxylated to give DA, which is subsequently converted to / -NE by p-hydroxylation. DA is a vital neurotransmitter in the central nervous system (CNS) and has actions on the kidneys and heart. Norepinephrine is also present as a neurotransmitter in the CNS, and is the principal neurotransmitter of the peripheral sympathetic nervous system. Epinephrine, which is elaborated from / -NE by N-methylation in the adrenal medulla, has potent actions on the heart, smooth muscle, and other organs (/). 

The phenylalkylamine hallucinogens show a close structural resemblance to the catecholamines, noradrenahne and dopamine. The prototype structure is found in mescaline, a naturally occurring substance. Modification of the mescaline molecule has led to synthetic amphetamine derivatives with hallucinogenic action. 

The adrenomimetic drugs can be divided into two major groups on the basis of their chemical structure the catecholamines and the noncatecholamines. The catecholamines include norepinephrine, epinephrine, and dopamine, all of which are naturally occurring, and several synthetic substances, the most important of which is isoproterenol (isopropyl norepinephrine). The skele-... 

Another naturally occurring drug that is similar to amphetamine can be found in the cactus Lophophora williamsii. Extracts are used to prepare a drink called peyote that contains 3,4,5-trimethoxyphenyl-ethylamine(the meth and phenyl point to a molecule that is quite lipid soluble). Known as mescaline, this compound is structurally similar to the catecholamines dopamine and norepinephrine but seems to act more directly upon serotonin receptors because of the presence of the meth-oxy groups on the molecule. This feature of the compound s structure would make the compound more fat-soluble and therefore better able to enter the brain quickly and may explain... 

The most well known of the naturally occurring phenethylamine derivatives (Table I) are the transmitters of the sympathetic nervous system, epinephrine, norepinephrine, and dopamine. All these compounds are 3,4-dioxygenated in the aromatic nucleus and are collectively known as the catecholamines. Norepinephrine is the transmitter of most sympathetic postganglionic fibers, dopamine is the predominant transmitter of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways, and epinephrine is the major hormone of the adrenal medulla (363). The literature that has accumulated on the action of these compounds in higher animals is enormous. Metanephrine and normetanephrine are known from animals as deactivated metabolites of epinephrine and norepinephrine that result from the action of the enzyme catechol O-methyltransferase (364). 

Biogenic amines, biological amines biologically and pharmacologically important naturally occurring amines, occurring widely in plants and animals. They can be divided into 1. derivatives of ethanolamine, e.g. choline, acetylcholine, muscarine 2. polymethylene diamines, e.g. putrescine, cadaverine 3.polyamines, e.g. spermine 4. imidazolylalkylamines, e.g. histamine 5.phenylalkylamines, e.g. mescaline, tyra-mine, hordenine 6. catecholamines, e. g. adrenalin, nor-adrenalin and dopamine 7. indolylalkylamines, e.g. tryptamine, serotonin and 8. betaines, e.g. carnitine. 

Epinephrine [ep ee NEF rin] is one of five catecholamines—epinephrine, norepinephrine, dopamine, dobutamine, and isoproterenol—commonly used in therapy. The first three catecholamines occur naturally, the latter two are synthetic compounds (see Figure 6.7). Epinephrine is synthesized from tyrosine in the adrenal medulla and released, along with small quantities of norepinephrine, into the blood stream. Epinephrine interacts with both a and p receptors. At low doses, p effects (vasodilation) on the vascular system predominate, whereas at high doses, a effects (vasoconstrictor) are strongest. 

The enzymes involved in the formation of the catecholamines are of low specificity. DOPA decarboxylase, or an enzyme closely akin to it, is concerned in the formation of 5-hydroxytryptamine > dopamine-/9-oxidase has been shown to be capable of hydroxylating the jd-carbon atom of a number of tyramine derivatives - and phenylethanolamine A-methyltransferase is equally unselective in its A-methylation of noradrenaline derivatives . This lack of specificity suggests the possibility that alternative pathways for the formation of noradrenaline and adrenaline might exist in vivo. Some of the putative intermediaries in these other pathways have been shown to occur naturally and one of them, octopamine (/) is found in the brain . 

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